Suppositories comprising cannabinoids

ABSTRACT

This invention relates to a suppository composition comprising cannabinoids. The suppository composition is formulated for easy absorption through mucosal membrane. The suppository as provided herein is useful for administration of cannabinoids in patients with nausea, vomiting, other conditions preventing swallowing, or conditions wherein suppository administration is required. Methods to manufacture the suppository composition are provided. Methods to treat pain, nausea, post-operative ileus and/or inflammatory bowel diseases using the suppository according to this invention are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/787,978, filed Oct. 19, 2017, which claims the benefit of U.S.Provisional Application No. 62/411,067, filed Oct. 21, 2016. Each of theabove-referenced patent applications is incorporated by reference in itsentirety.

BACKGROUND OF THE INVENTION Field of the Invention

This invention relates to suppository formulations for medical use. Thesuppository may be applied to human cavities other than the oral cavity.This suppository provides efficient absorption of active ingredientswhile avoiding unpleasant taste and/or vomiting.

DESCRIPTION OF THE RELATED TECHNOLOGY

The cannabis plant has many naturally occurring substances that are ofgreat interest in the fields of science and medicine. Isolated compoundsfrom the cannabis plant include Δ⁹-tetrahydrocannabinol (THC),cannabidiol (CBD), cannabichromene (CBC), cannabigerol (CBG),cannabidivarin (CBDV), among other compounds. While THC has psychoactiveeffects, CBD, CBC, CBG, and CBDV do not. Isolated compounds from thecannabis plant are called cannabinoids. There are a total of one hundredand forty one (141) cannabinoids that have been isolated from thecannabis plant. Many researchers have confirmed the medicinal value ofcannabinoids. Cannabinoids have been investigated for possible treatmentof seizures, nausea, vomiting, lack of appetite, pain, arthritis,inflammation, and other conditions.

Cannabinoids can be isolated by extraction or cold pressing fromcannabis plants. Plants in the cannabis genus include Cannabis saliva,Cannabis ruderalis, and Cannabis indica. These plants are naturalsources of cannabinoids. Cannabinoids are also available in syntheticforms. Methods to synthesize cannabinoids in lab settings werediscovered and are still currently practiced. Synthetic cannabinoids aremore targeted, in that the synthetic compound usually comes isolatedwithout other cannabinoids mixed in.

Nabilone(racemic(6aR,10aR)-1-hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-7,8,10,10a-tetrahydro-6H-benzo[c]chromen-9(6aH)-one),a synthetic cannabinoid, is believed to have fewer undesired sideeffects than THC. Nabilone mimics the chemical compound structure ofTHC. THC also exists in synthetic form under the name Dronabinol((-)-(6aR,10aR)-6,6,9-trimythel-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol)).These synthetic cannabinoids are sold for food supplement purposes andare being investigated for medicinal purposes. The U.S. Food and DrugAdministration approved nabilone for treatment of chemotherapy-inducednausea and vomiting. In the United States, nabilone is marketed underthe name Cesamet®.

The IUPAC nomenclature of THC is(-)-(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1ol.CBD's IUPAC nomenclature is 2-((1S,6S)-3-methyl-6-(prop-1-en-2-yl)cyclo-hex-2-enyl)-5-pentylbenzene-1,3-diol).CBC has the IUPAC nomenclature of2-methyl-2-(4-methylpent-3-enyl)-7pentyl-5-chromenol. CBG has the IUPACnomenclature of2-[(2E)-3,7-dimethylocta-2,6-dienyl]-5-pentyl-benzene-1,3-diol. Theseare among the most prominent compounds in the family of compoundsextracted from the cannabis plant referred to as cannabinoids.

Cannabidiol is a major phytocannabinoid, accounting for up to 40% of theplant's extract. CBD is a CB-1 receptor antagonist, while THC is a CB-1receptor agonist. A 2010 research found that cannabis strains withhigher concentration of CBD did not produce the short-term memoryimpairment normally seen in high THC cannabis strains, a characteristicattributed to the CB-1 receptor antagonist nature of CBD. CBD isconsidered to have a wider scope of medical applications than THC.

Because it is a relatively unknown cannabinoid, cannabigerol (CBG)remains understudied and its effects are only just starting to becomeclear. CBG is a non-psychoactive cannabinoid found in the cannabisplant. All cannabinoids in the early stage of the cannabis plant's lifebegins as CBG. CBG is found in higher concentrations in hemp plants asopposed to marijuana plants, which are grown to have higherconcentrations of tetrahydrocannabinol (THC). CBG has been found to actas a high affinity α₂-adrenergic receptor agonist, a moderate affinity5-HT_(1A) receptor antagonist, and a low affinity CB₁ receptorantagonist. It binds with the CB₂ receptor, but it is currently unknownwhether it acts as an agonist or antagonist.

Cannabis abuse can occur among chronic users, especially when raw plantmaterials are consumed by smoking. Collectively, this abuse is referredto as cannabis use disorder. Discontinuance of cannabis consumption canresult in withdrawal symptoms. However, some cannabinoids, such as CBD,may be useful in treating cannabis use disorder. Various methods todeliver CBD or other cannabinoids are available, aiming at avoidinginhalation of burning materials.

Suppository is a solid medical preparation in a roughly conical orcylindrical shape, designed to be inserted into the rectum or vagina todissolve. Suppository may be used in administration of certainmedications wherein administration via other routes is impractical,ineffective, or too invasive. Suppository is also preferred where themedication's action location is close to the rectum or the vagina andabsorption through the mucosal membrane is effective. Suppository isalso recommended when the active ingredient is easily degraded ingastric fluid or tastes too bad.

Suppository melts inside body cavities by the body's temperature and thepresence of bodily fluid. Covers suitable for dissolution are gelatin orcocoa butter. Upon dissolution, active ingredients are absorbed throughthe mucosal membrane lining the body cavity.

SUMMARY

This invention provides a suppository composition comprisingcannabinoids, a fatty base, a non-ionic surfactant, and a sugar alcoholor sugar. Cannabinoids may be CBD, CBG, CBN, THC, CBDV, or THCV, or acombination of all or some of these. Sugar alcohols may be isomalt,mannitol, sorbitol, xylitol, lactitol, maltitol, or erythritol. Sugarsmay be dextrose, maltose, fructose, or sucrose. Fatty bases may beceteareth-15, glycerol ricinoleate, or hydrogenated coco-glycerin, amongother suitable fatty bases, which may be sold under the brands WitepsolS58, Witepsol H15, or Witepsol H58. Non-ionic surfactants may beceteareth-15, ceteareth-17, or ceteareth-25. Methods to manufacture anduse the suppository composition are also provided.

This invention provides a suppository composition comprising:

-   -   at least one cannabinoid at 0.1% to 50% by weight of the total        composition;    -   at least one sugar alcohol or sugar at 15% to 25% by weight of        the total composition;    -   at least one fatty base suitable for suppository formulation at        60% to 80% by weight of the total composition; and    -   at least one non-ionic surfactant at 2% to 10% by weight of the        total composition,    -   wherein the composition is packaged in a suppository mold.

The invention provides a suppository composition as above wherein the atleast one cannabinoid is CBD, CBG, CBN, CBDV, and THCV.

The invention provides a suppository composition as above wherein the atleast one cannabinoid is THC and wherein THC comprises 0.1% to 2% byweight of the total composition.

The invention provides a suppository composition as above wherein the atleast one cannabinoid is from natural sources or synthetic.

The invention provides a suppository composition as above wherein the atleast one cannabinoid is nanoencapsulated.

The invention provides a suppository composition as above wherein theparticles are of size 20 -40 nm.

The invention provides a suppository composition as above, wherein theat least one cannabinoid is encapsulated into hyaluronic acidderivatives nanolattice.

The invention provides a suppository composition as above, wherein theat least one cannabinoid is encapsulated into hyaluronic acidderivatives and tocopherol nanolattice.

The invention provides a suppository composition as above wherein thehyaluronic acid derivatives is sodium oleyl hyaluronate.

The invention provides a suppository composition as above, wherein theat least one sugar is selected from the group consisting of dextrose,maltose, fructose, and sucrose wherein the at least one sugar isprovided in micronized form.

The invention provides a suppository composition as above, wherein theat least one sugar alcohol is selected from the group consisting ofisomalt, mannitol, sorbitol, xylitol, lactitol, maltitol, and erythritoland wherein the at least one sugar alcohol is provided in micronizedform.

The invention provides a suppository composition as above, wherein theat least one non-ionic surfactants may be selected from the groupconsisting of ceteareth-15, ceteareth-17, and ceteareth-25.

The invention provides a suppository composition as above, wherein theat least one fatty base is selected from the group consisting ofricinoleate, hydrogenated coco-glycerin, and ceteareth-25.

This invention provides a method to treat or alleviate nausea orvomiting, comprising administering the suppository according to claim 1to a mammal 1-6 times a day as needed.

This invention provides a method to treat or alleviate nausea accordingto embodiments, wherein the nausea or vomiting is chemotherapy relatednausea or vomiting.

This invention provides a method to treat or alleviate pain, comprisingadministering the suppository according to claim 1 to a mammal 1-6 timesa day or as needed.

This invention provides a method to treat or alleviate pain according toembodiments, wherein the pain is menstrual pain.

This invention provides a method to treat or alleviate post-operativeileus, comprising administering the suppository according to claim 1 toa mammal 1-6 times a day or as needed.

This invention provides a method to treat or alleviate intestinalinflammation, comprising administering the suppository according toclaim 1 to a mammal 1-6 times a day or as needed.

This invention provides a method to treat or alleviate intestinalinflammation according to embodiments, wherein the intestinalinflammation is irritable bowel syndrome or inflammatory bowel disease.

ABBREVIATIONS

CBC: Cannabichromene

CBD: Cannabidiol

CBDV: Cannabidivarin

CBG: Cannabigerol

CBN: Cannabinol

IUPAC: International Union of Pure and Applied Chemistry

THC: Tetrahydrocannabinol

THCV: Tetrahydrocannabidivarin

DETAILED DESCRIPTION OF CERTAIN INVENTIVE EMBODIMENTS

Embodiments of this application relate to a suppository compositioncomprising cannabinoids. Various cannabinoids may be incorporated intothis suppository for effective absorption. Suppositories provide forabsorption of active ingredients such as cannabinoids where oralapplication is ineffective, especially when the subject suffers fromnausea or in uncooperative minors. A method to treat pain and nausea isalso provided.

The word “cannabinoid” used in this description, claims, and otherconjugations is used to mean any compound that interacts with acannabinoid receptor and other cannabinoid mimetics, including, but notlimited to, certain tetrahydropyran analogs (Δ⁹- tetrahydrocannabinol,Δ⁸-tetrahydrocannabinol,6,6,9-trimythel-3-pentyl-6H-dibenzo[b,d]pyran-1-ol,3-(1,1-dimethylheptyl)-6,6a7,8,10,10a-hexahydro-1-1hydroxy-6,6-dimythel-9H-dibezo[b,d]pyran-9-ol,(-)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol-1,1-dimethylheptyl,(+)-(3S,4S)-7-hydroxy-Δ-6-tetrahydrocannabinol, andΔ⁸-tetrahydrocannabinol-11-oic acid); certain piperidine analogs (e.g.,(-)-(6S,6aR,9R,10aR)-5,6,6a,7,8,9,10,10a-octahydro-6-methyl-1-3-[(R)-1-methyl-4-phenylbutoxy]-1,9-phenanthridinediol 1-acetate));certain aminoalkylindole analogs (e.g.,(R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylm-ethyl)-pyrrolo[1,2,3,-de]-1,4-benzoxazin-6-yl]-1-naphthelenyl-methanone); certain open pyran-ringanalogs (e.g.,2-[3-methyl-6-(1-methylethenyl-2-cyclohexen-1-yl]-5-pentyl-1,3-benzendi-ol,and 4-(1,1- dimethylheptyl)-2,3′-dihydroxy-6′-α-(3-hydroxypropyl)-1′,2′,3′,4′,5′,6′-hexahydrobiphenyl),their salts, solvates, metabolites, and metabolic precursors.

The word “cannabidiol” refers to cannabidiol and cannabidiolderivatives. As used in this application, cannabidiol is obtained fromindustrial hemp extract with a trace amount of THC or from cannabisextract using high-CBD cannabis cultivars. Alternatively, synthetic CBDmay also be used.

The word “tetrahydrocannabinol” refers to tetrahydrocannabinol andtetrahydrocannabinol derivatives. As used in this application,tetrahydrocannabinol is obtained from cannabis extract. Alternatively,synthetic THC may also be used.

The word “cannabigerol” refers to cannabigerol and cannabigerolderivatives. As used in this application, cannabigerol is obtained fromindustrial hemp extract or from cannabis extract using high-CBG cannabiscultivars with a trace amount of THC and other cannabinoids.Alternatively, synthetic CBG may also be used.

In embodiments, cannabinoids may be provided as crystallizedcannabinoids in solid form. Solid cannabinoids may be obtained fromnatural sources by freeze drying and/or heating of cannabis oil or hempoil. Alternatively, solid cannabinoids may be obtained from syntheticsources. Methods to synthesize cannabinoids are disclosed in PatentApplication Publication US2010/0298579 by THC Pharm GmbH and thisreference is included herein as a whole.

Cannabinoids may also be in oily form, as cannabis oil, hemp oil, orhashish oil. In these embodiments, emulsion formulation for thesuppository content may have cannabinoids dispersed throughout theemulsion for better absorption. It is contemplated that cannabinoidsprovided in oily form may be used in the embodiments described herein.

In embodiments, cannabinoids may be procured from natural sources, wheremore than one cannabinoid may be present. Cannabinoids may also beprocured from synthetic sources and a plurality of syntheticcannabinoids may be used in this suppository composition. At least onecannabinoid may be present in this suppository composition.

In embodiments, cannabinoids may also be provided in microencapsulationor nanoencapsulation form into particles. Encapsulation may result incannabinoids and other materials present in cannabinoid materials inliposomal capsule particles or other types of particles.

Microencapsulation or nanoencapsulation may increase cannabinoidbioavailability by up to 4 times, thereby increasing cannabinoidefficacy after absorption through the mucosal membrane.Microencapsulation or nanoencapsulation may result in particles of 20-40nm in size. Microencapsulation or nanoencapsulation promotes dissolutionof cannabinoid particles in an aqueous environment.

In embodiments, cannabinoids may be nanoencapsulated into hyaluronicacid (HA) derivatives nanolattice. Additionally, cannabinoids may alsobe nanoencapsulated into a combination of hyaluronic acid derivativesand tocopherol nanolattice. Hyaluronic acid derivatives nanolattice mayinclude but is not limited to sodium oleyl hyaluronate.

Cannabinoids as used in these embodiments may be CBD, CBG, CBN, THC,CBDV, THCV, or other molecules within the cannabinoid family. Acombination of cannabinoids may be used in these embodiments, such thatthe total amount of cannabinoids comprises the quantities as described.

In embodiments, the suppository composition may comprise at least onecannabinoid, such as CBD, CBG, THC, derivatives thereof, or acombination of cannabinoids. Other cannabinoids suitable for use in thissuppository composition may be CBN, CBDV, or THCV, or a combinationthereof, among other cannabinoids.

In embodiments, the total amount of cannabinoids may be at 0.1% to 50%by total weight of the suppository composition. Total amount ofcannabinoids may comprise different cannabinoids at different ratios.The total amount of THC may be at a lower weight percentage to minimizepsychoactive effect.

The total amount of THC in embodiments may be at 0.1% to 2% by weight ofthe total composition. In a 2 gram suppository, THC may be at 2-40 mg.The total amount of cannabinoids other than THC may be at 0.1% to 5% byweight of the total composition. In a 2 gram suppository, cannabinoidsother than THC may be at 2-100 mg. Where a combination of cannabinoidsis used, total THC level may be between 0.1% to 2% by weight of thetotal composition and the total amount of all cannabinoids in asuppository composition may not exceed 50% by weight.

In embodiments, the suppository composition may comprise at least onewater-soluble sugar alcohol or sugar. Suitable sugar alcohols may beisomalt, mannitol, sorbitol, xylitol, lactitol, maltitol, or erythritol.Suitable sugars may be dextrose, maltose, fructose, or sucrose. Sugaralcohol or sugar in these embodiments may comprise 15% to 25% by weightof the total composition. A combination of sugar alcohols and/or sugarsmay also be used. Sugar alcohols or sugars may be provided in micronizedform to promote dissolution.

In embodiments, the suppository composition may comprise at least onefatty base of pharmaceutical grade for suppository formulations. Fattybases may comprise fatty acids suitable for absorption through mucosalmembranes, such as glycerol ricinoleate, hydrogenated coco-glycerin, andceteareth-25. Fatty bases may be commercially available, such asWitepsol S58 sold by Cremer Health, or Witepsol H15, Witepsol H85, orother suitable fatty bases for suppository formulation.

Fatty bases for a suppository formulation as above may provide for ahydrophobic environment wherein cannabinoids may disperse. Apart fromproviding an environment for dispersion, fatty bases may also bulk upthe formulation as a whole to provide for encapsulation in asuppository. Fatty bases in embodiments may comprise 60% to 80% byweight of the total composition. A combination of suitable fatty basesmay also be used.

In embodiments, the suppository may further comprise at least onenon-ionic surfactant to provide an emulsifier to promote equaldispersion of cannabinoids. Suitable non-ionic surfactants may bevarious ceteareth-n, which may be cetyl alcohol (ceteareth-15), stearylalcohol (ceteareth-17), or ceteareth-25. Non-ionic surfactants maycomprise 2% to 10% by weight of the total composition.

In embodiments, the suppository composition may be manufactured by firstblending at least one cannabinoid in solid or liquid form with at leastone non-ionic surfactant under a nitrogen blanket in a fluid bedreactor. A fluid bed reactor may cause the cannabinoids and non-ionicsurfactant to behave as a liquid during manufacturing of the suppositoryformulation.

The manufacture process may further comprise spraying at least onenon-ionic surfactant such as ceteareth-25 at about 50° C. into thecannabinoid-sugar alcohol or cannabinoid-sugar particles. Since thecannabinoid-sugar alcohol or cannabinoid-sugar particles are in thefluid bed reactor, the spraying also happens in this environment. Theblend may then be cooled to room temperature while a N₂ stream is purgedinto the mixture.

A fatty base may be melted in a different vessel at about 70° C. in aseparate vessel. Once melted, the cannabinoid-sugar alcohol orcannabinoid-sugar particles may be added into the vessel and the mixturemay be stirred until homogenous while the mixture is kept at 70° C. Themixture may be continuously stirred while allowed to cool down.

The mixture from the step above may be poured into suppository moldsbefore re-solidification. Upon closing of the suppository molds, thesuppositories may be allowed to cool to room temperature. Thesuppositories may then be packed into air and moisture tight suppositoryblisters.

Suppositories may in conical, bullet, or round shape. A suppository mayhave an outside coating layer to promote dissolution by contact with themucosal membrane and by the body's temperature. The outside coatinglayer may be by cocoa butter or gelatin from animal or plant sources.

In embodiments, the suppositories may be administered to a subject inneed thereof by placing into cavities such as the rectum or the vagina.The suppositories may be held in the appropriate cavities for absorptionuntil fully absorbed.

The suppository according to embodiments may be used in treatment oralleviation of nausea and/or vomiting. A mammal, such as a human being,may receive the suppository composition according to embodiments 1-6times a day or as needed for nausea treatment.

The suppository according to embodiments may be used in treatment oralleviation of chemotherapy related nausea and vomiting. A mammal, suchas a human being, may receive the suppository composition according toembodiments 1-6 times a day or as needed for treatment of chemotherapyrelated nausea and vomiting.

The suppository according to embodiments may be used in treatment oralleviation of pain and/or chronic pain. A mammal, such as a humanbeing, may receive the suppository composition according to embodiments1-6 times a day or as needed for pain treatment.

The suppository according to embodiments may be used in treatment oralleviation of menstrual cramps or pain. A mammal, such as a humanbeing, may receive the suppository composition according to embodiments1-6 times a day or as needed for menstrual cramp pain treatment.

The suppository according to embodiments may be used in treatment oralleviation of post-operative ileus. A mammal, such as a human being,may receive the suppository composition according to embodiments 1-6times a day or as needed for treatment of post-operative ileus.

The suppository according to embodiments may be used in treatment oralleviation of intestinal inflammation such as irritable bowel syndrome(MS), irritable bowel disease (IBD), such as ulcerative colitis and/ orCrohn's disease. A mammal, such as a human being, may receive thesuppository composition according to embodiments 1-6 times a day or asneeded for treatment of intestinal inflammation such as IBS or IBD(Crohn's disease, ulcerative colitis).

EXAMPLES

Suppository pill preparation

A suppository having 20 mg of CBD is prepared. Percentages are given inweight percentage.

TABLE 1 Phase Raw Material Percentage (%) A1 Witepsol S58 70 A2Ceteareth 25 5 A3 Hemp oil having CBD at 20% weight 5 (nanoencapsulated)A4 Micronized isomalt 20 Total 100

Witepsol S58 is obtained from IOI Oleochemical GmbH, having as its majorcomponents hydrogenated coco-glycerides, ceteareth-25, and glycerylricinoleate. Hemp oil having CBD at 20% weight and other minor amount ofcannabinoids naturally occurring in hemp oil is nanoencapsulated.

Obtain ingredients according to the above percentage. Make a blend ofPhase A3 and A4 under a nitrogen blanket in a fluid bed reactor. SprayPhase A2 at 50° C. on to the mixture above (cannabinoid-isomaltparticles) in the fluid bed reactor. Cool the blend to room temperaturewhile purging under nitrogen. Melt Phase A1 in a separate vessel at 70°C., and then add the mixture above into Phase A1. Stir the mixture at70° C. until homogenous. Cool the mixture down while continuouslystirring.

Before re-solidification, pour the mixture into suppository molds, andthen cool the molds to room temperature. The suppositories may be of amass of about 2 gram each. The suppositories may then be packed into airand moisture tight suppository blisters.

A suppository with a mass at about 2 gram and containing 20 mg CBD isprepared.

All references, including publications, patent applications, and patentscited herein are hereby incorporated by reference to the same extent asif each reference were individually and specifically indicated to beincorporated by reference and were set forth in its entirety herein.

It will be readily apparent to those skilled in the art that a number ofmodifications and changes may be made without departing from the spiritand the scope of the present invention. It is to be understood that anyranges, ratios, and range of ratios that can be derived from any of thedata disclosed herein represent further embodiments of the presentdisclosure and are included as part of the disclosure as though theywere explicitly set forth. This includes ranges that can be formed thatdo or do not include a finite upper and/or lower boundary. Accordingly,a person of ordinary skill in the art will appreciate that such valuesare unambiguously derivative from the data presented herein.

What is claimed is:
 1. A suppository composition comprising: at leastone cannabinoid at 0.1% to 50% by weight of the total composition; atleast one sugar alcohol or sugar at 15% to 25% by weight of the totalcomposition; at least one fatty base suitable for suppositoryformulation selected from the group consisting of glycerol ricinoleate,hydrogenated coco-glycerin, and ceteareth-25 at 60% to 80% by weight ofthe total composition; and at least one non-ionic surfactant selectedfrom the group consisting of ceteareth-15 and ceteareth-17 at 2% to 10%by weight of the total composition, wherein the at least one cannabinoidis nanoencapsulated into particles, and wherein the composition ispackaged in a suppository mold.
 2. The suppository composition of claim1, wherein the at least one cannabinoid is selected from the groupconsisting of CBD, CBG, CBN, CBDV, and THCV.
 3. The suppositorycomposition of claim 1, wherein the at least one cannabinoid is THC andwherein THC comprises 0.1% to 2% by weight of the total composition. 4.The suppository composition of claim 1, wherein the at least onecannabinoid is from natural sources or synthetic.
 5. The suppositorycomposition of claim 1, wherein the particles are of size 20-40 nm. 6.The suppository composition of claim 1, wherein the at least onecannabinoid is encapsulated into hyaluronic acid derivativesnanolattice.
 7. The suppository composition of claim 6, wherein thehyaluronic acid derivatives is sodium oleyl hyaluronate.
 8. Thesuppository composition of claim 1, wherein the at least one sugar isselected from the group consisting of dextrose, maltose, fructose, andsucrose.
 9. The suppository composition of claim 1, wherein the at leastone sugar is provided in micronized form.
 10. The suppositorycomposition of claim 1, wherein the at least one sugar alcohol isselected from the group consisting of isomalt, mannitol, sorbitol,xylitol, lactitol, maltitol, and erythritol.
 11. The suppositorycomposition of claim 1, wherein the at least one sugar alcohol isprovided in micronized form.
 12. A method to treat or alleviate nauseaor vomiting, comprising administering the suppository of claim 1 to amammal 1-6 times a day as needed.
 13. The method of claim 12, whereinthe nausea or vomiting is chemotherapy related nausea or vomiting.
 14. Amethod to treat or alleviate pain, comprising administering thesuppository of claim 1 to a mammal 1-6 times a day or as needed.
 15. Themethod of claim 14, wherein the pain is menstrual pain.
 16. A method totreat or alleviate post-operative ileus, comprising administering thesuppository of claim 1 to a mammal 1-6 times a day or as needed.
 17. Amethod to treat or alleviate intestinal inflammation, comprisingadministering the suppository of claim 1 to a mammal 1-6 times a day oras needed.
 18. The method of claim 17, wherein the intestinalinflammation is irritable bowel syndrome or inflammatory bowel disease.